share

Split Response to Steroids

In mammals, a single gene encodes the receptor for the steroid reproductive hormone progesterone, but the protein exists in two forms, progesterone receptor-A (PR-A) and PR-B, that result from alternative starting points for transcription and translation. Mulac-Jericevic et al. describe mice in which a mutation selectively prevents expression of PR-A. Acting alone, PR-B regulated only a subset of known progesterone-responsive genes in the uterus. Progesterone normally antagonizes estrogen-induced proliferation in the uterine epithelium, yet interactions with PR-B promoted proliferation. The separation of distinct physiological functions for PR-A and PR-B raises the possibility that selective modulators of the PR isoforms could provide more specific therapeutic effects.